Pub Date : 2025-12-01DOI: 10.1016/j.isci.2025.114301
Sridevi Venkatesan , Daria Nazarkina , Megan T. Sullivan , Yao-Fang Tan , Sarah Qu , Amy J. Ramsey , Evelyn K. Lambe
Mutations in N-methyl-D-aspartate receptors (NMDARs) cause epilepsy and profound cognitive impairment, though the underlying subunit-specific vulnerabilities remain unclear. We investigate the impact of a severe human variant in the lurcher motif of obligate GluN1 NMDAR subunit using transgenic mice, revealing unexpected context-dependent phenotypes. We show that the GluN1 Y647S variant significantly reduces current flow through pharmacologically isolated synaptic NMDARs in prefrontal neurons. Yet in intact local circuits, this loss-of-function paradoxically extends NMDAR-dependent dendritic integration, causing prolonged circuit-wide excitation that promotes seizures. Mutant receptors appear deficient in engaging opposing dendritic ion channels that normally curtail NMDAR-dependent excitation. Boosting SK channel activity normalizes dendritic integration, whereas slight decreases in extracellular magnesium further extend abnormally prolonged integration in mutant mice. We find that magnesium supplementation successfully treats seizures in vivo in the transgenic mice, despite loss-of-function of NMDARs. Overall, we disentangle a GluN1 variant’s receptor-level effects and its dendritic impact to treat seizures effectively.
n -甲基- d -天冬氨酸受体(NMDARs)的突变导致癫痫和严重的认知障碍,尽管潜在的亚基特异性脆弱性尚不清楚。我们使用转基因小鼠研究了GluN1 NMDAR亚基专性lurcher基的严重人类变异的影响,揭示了意想不到的上下文依赖性表型。我们发现GluN1 Y647S变异显著降低了通过药理学分离的前额叶神经元突触NMDARs的电流。然而,在完整的局部电路中,这种功能丧失反而延长了nmdar依赖的树突整合,导致长时间的全回路兴奋,从而促进癫痫发作。突变受体似乎缺乏参与对立的树突离子通道,通常限制nmdar依赖的兴奋。增强SK通道活性使树突整合正常化,而细胞外镁的轻微减少进一步延长了突变小鼠异常延长的整合。我们发现,尽管NMDARs的功能丧失,但镁补充剂成功地治疗了转基因小鼠体内的癫痫发作。总的来说,我们解开了GluN1变体的受体水平效应及其对有效治疗癫痫发作的树突影响。
{"title":"Context-dependent NMDA receptor dysfunction predicts seizure treatment in mice with human GluN1 variant","authors":"Sridevi Venkatesan , Daria Nazarkina , Megan T. Sullivan , Yao-Fang Tan , Sarah Qu , Amy J. Ramsey , Evelyn K. Lambe","doi":"10.1016/j.isci.2025.114301","DOIUrl":"10.1016/j.isci.2025.114301","url":null,"abstract":"<div><div>Mutations in N-methyl-D-aspartate receptors (NMDARs) cause epilepsy and profound cognitive impairment, though the underlying subunit-specific vulnerabilities remain unclear. We investigate the impact of a severe human variant in the lurcher motif of obligate GluN1 NMDAR subunit using transgenic mice, revealing unexpected context-dependent phenotypes. We show that the GluN1 Y647S variant significantly reduces current flow through pharmacologically isolated synaptic NMDARs in prefrontal neurons. Yet in intact local circuits, this loss-of-function paradoxically extends NMDAR-dependent dendritic integration, causing prolonged circuit-wide excitation that promotes seizures. Mutant receptors appear deficient in engaging opposing dendritic ion channels that normally curtail NMDAR-dependent excitation. Boosting SK channel activity normalizes dendritic integration, whereas slight decreases in extracellular magnesium further extend abnormally prolonged integration in mutant mice. We find that magnesium supplementation successfully treats seizures <em>in vivo</em> in the transgenic mice, despite loss-of-function of NMDARs. Overall, we disentangle a GluN1 variant’s receptor-level effects and its dendritic impact to treat seizures effectively.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"29 1","pages":"Article 114301"},"PeriodicalIF":4.1,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145788827","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-01DOI: 10.1016/j.isci.2025.114275
Jiangchen Yao , Dingfa Deng , Han Yu , Junxia Duan , Shuyun Xia , Xunyu Cao , Yafeng Xie , Bibo Xie , Peng Ling , Feijun Zhao
As the reliability of nontreponemal tests for evaluating syphilis treatment efficacy is increasingly questioned, we propose an optimized approach using Treponema pallidum (Tp) antigens (Tp0134, Tp0768, Tp0971, Tp0462, and Tp92) combined with a machine learning (ML) model. Analysis of 509 serum samples (including paired pre- and post-treatment samples) employed an established ELISA assay to dynamically monitor antibody changes. Results demonstrated that post-treatment antibody reduction for potential infection-stage-dependent antigens (pIDAs) (especially Tp0134 and Tp0768) was markedly higher than for the non-infection-stage-dependent antigen Tp92 and traditional methods. Utilizing nested cross-validation to train an array of ML models, ultimately chosen random forest model (AUC = 0.815) demonstrated enhanced efficacy in accurately distinguishing between infection and cure. Specifically, Tp0768, Tp92, and Tp0134 were identified as the pivotal features. Combining Tp antigens with ML provides a more accurate and dynamic tool for treatment efficacy assessment, enabling a more effective evaluation of syphilis treatment outcomes in the future.
{"title":"A pilot study: Incorporating Treponema pallidum antigens into machine learning models for accurate syphilis treatment outcome assessment","authors":"Jiangchen Yao , Dingfa Deng , Han Yu , Junxia Duan , Shuyun Xia , Xunyu Cao , Yafeng Xie , Bibo Xie , Peng Ling , Feijun Zhao","doi":"10.1016/j.isci.2025.114275","DOIUrl":"10.1016/j.isci.2025.114275","url":null,"abstract":"<div><div>As the reliability of nontreponemal tests for evaluating syphilis treatment efficacy is increasingly questioned, we propose an optimized approach using <em>Treponema pallidum</em> (Tp) antigens (Tp0134, Tp0768, Tp0971, Tp0462, and Tp92) combined with a machine learning (ML) model. Analysis of 509 serum samples (including paired pre- and post-treatment samples) employed an established ELISA assay to dynamically monitor antibody changes. Results demonstrated that post-treatment antibody reduction for potential infection-stage-dependent antigens (pIDAs) (especially Tp0134 and Tp0768) was markedly higher than for the non-infection-stage-dependent antigen Tp92 and traditional methods. Utilizing nested cross-validation to train an array of ML models, ultimately chosen random forest model (AUC = 0.815) demonstrated enhanced efficacy in accurately distinguishing between infection and cure. Specifically, Tp0768, Tp92, and Tp0134 were identified as the pivotal features. Combining Tp antigens with ML provides a more accurate and dynamic tool for treatment efficacy assessment, enabling a more effective evaluation of syphilis treatment outcomes in the future.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"29 1","pages":"Article 114275"},"PeriodicalIF":4.1,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145735576","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-01DOI: 10.1016/j.isci.2025.114284
Petra den Hollander , Maria Castaneda , Suhas V. Vasaikar , Joanna Joyce Maddela , Claire Gould , Breanna R. Demestichas , Robiya Joseph , Shivangi Agarwal , Abhijeet P. Deshmukh , Alvina Zia , Shruti Shah , Tieling Zhou , Geraldine Raja , Paul Allegakoen , Nick A. Kuburich , Mika Pietila , Chunxiao Fu , Jeffrey Chang , Chad J. Creighton , William F. Symmans , Sendurai A. Mani
Epithelial-to-mesenchymal transition (EMT) is known to induce both stemness and mesenchymal properties, and our findings reveal that these two programs can be uncoupled. During EMT, epithelial cells transition from symmetric divisions producing differentiated daughter cells to self-renewing daughter cells. When we block cell division and induce EMT, cells gain mesenchymal properties but not stemness, suggesting the importance of cell division for gaining stemness. We identified ESRP1 as a key regulator of EMT-driven stemness, which get downregulated during EMT in a cell division-dependent manner. Overexpression of ESRP1 prevents the gain of stemness without affecting the mesenchymal program. Only the stemness and not the mesenchymal signature, induced during EMT, correlates with poor prognosis. All cancer cells with stemness properties exhibit mesenchymal properties, but not all mesenchymal cells exhibit stemness properties. In summary, during EMT the stemness program is controlled by cell division and ESRP1, and this program predicts poor prognosis.
{"title":"EMT-induced stem cell and mesenchymal programs can be decoupled via cell division and ESRP1-dependent mechanisms","authors":"Petra den Hollander , Maria Castaneda , Suhas V. Vasaikar , Joanna Joyce Maddela , Claire Gould , Breanna R. Demestichas , Robiya Joseph , Shivangi Agarwal , Abhijeet P. Deshmukh , Alvina Zia , Shruti Shah , Tieling Zhou , Geraldine Raja , Paul Allegakoen , Nick A. Kuburich , Mika Pietila , Chunxiao Fu , Jeffrey Chang , Chad J. Creighton , William F. Symmans , Sendurai A. Mani","doi":"10.1016/j.isci.2025.114284","DOIUrl":"10.1016/j.isci.2025.114284","url":null,"abstract":"<div><div>Epithelial-to-mesenchymal transition (EMT) is known to induce both stemness and mesenchymal properties, and our findings reveal that these two programs can be uncoupled. During EMT, epithelial cells transition from symmetric divisions producing differentiated daughter cells to self-renewing daughter cells. When we block cell division and induce EMT, cells gain mesenchymal properties but not stemness, suggesting the importance of cell division for gaining stemness. We identified ESRP1 as a key regulator of EMT-driven stemness, which get downregulated during EMT in a cell division-dependent manner. Overexpression of ESRP1 prevents the gain of stemness without affecting the mesenchymal program. Only the stemness and not the mesenchymal signature, induced during EMT, correlates with poor prognosis. All cancer cells with stemness properties exhibit mesenchymal properties, but not all mesenchymal cells exhibit stemness properties. In summary, during EMT the stemness program is controlled by cell division and ESRP1, and this program predicts poor prognosis.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"29 1","pages":"Article 114284"},"PeriodicalIF":4.1,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145788987","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-01DOI: 10.1016/j.isci.2025.114295
Hongjuan Zhang , Haibing Liu , Rongkai Chen
Innovation networks drive technological progress, yet their multilayer structures remain poorly understood in digital economy vulnerability contexts. This study develops a comprehensive framework for assessing multilayer innovation network resilience, analyzing interdependencies and disruption scenarios using China’s digital economy as a representative empirical context. We construct coupled multilayer networks implementing four integrated attack strategies to identify cascading vulnerability mechanisms. Results reveal asymmetric patterns: collaboration networks show significant fragility to targeted attacks, while knowledge networks demonstrate higher resilience, especially during mature stages. Cascade failure analysis establishes that knowledge network disruptions propagate severe ecosystem-wide effects, whereas collaboration network perturbations generate limited cross-layer impacts. This asymmetry advances multilayer innovation network theory and provides practical insights for vulnerability assessment. The framework indicates that protecting critical technological knowledge should prioritize over maintaining collaborative arrangements when resources are limited, as knowledge networks constitute the essential integrative mechanism within innovation systems.
{"title":"Multilayer innovation network resilience: A framework for digital economy vulnerability assessment","authors":"Hongjuan Zhang , Haibing Liu , Rongkai Chen","doi":"10.1016/j.isci.2025.114295","DOIUrl":"10.1016/j.isci.2025.114295","url":null,"abstract":"<div><div>Innovation networks drive technological progress, yet their multilayer structures remain poorly understood in digital economy vulnerability contexts. This study develops a comprehensive framework for assessing multilayer innovation network resilience, analyzing interdependencies and disruption scenarios using China’s digital economy as a representative empirical context. We construct coupled multilayer networks implementing four integrated attack strategies to identify cascading vulnerability mechanisms. Results reveal asymmetric patterns: collaboration networks show significant fragility to targeted attacks, while knowledge networks demonstrate higher resilience, especially during mature stages. Cascade failure analysis establishes that knowledge network disruptions propagate severe ecosystem-wide effects, whereas collaboration network perturbations generate limited cross-layer impacts. This asymmetry advances multilayer innovation network theory and provides practical insights for vulnerability assessment. The framework indicates that protecting critical technological knowledge should prioritize over maintaining collaborative arrangements when resources are limited, as knowledge networks constitute the essential integrative mechanism within innovation systems.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"29 1","pages":"Article 114295"},"PeriodicalIF":4.1,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145736037","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Convolvulus pluricaulis (shankhpushpi) is a traditional herb used to treat depression and anxiety. Using Drosophila melanogaster as a model, we identified conserved metabolic and molecular pathways mediating its neuroprotective effects. Metabolomic profiling of flies fed C. pluricaulis revealed altered levels of ascorbic acid, glucose, and adenine monophosphate in the head tissue. Gene expression analysis showed significant modulation of Glut1 (glucose transporter 1), CG6293 (ascorbate transporter), Rdl (resistant to dieldrin), GABA-B-R1 (GABA-B receptor 1), and Sod1 (superoxide dismutase 1). Dietary C. pluricaulis reduced depression-like behavior in a stress-induced model and elevated head ascorbate levels. Knockdown of CG6293, Sod1, Glut1, or GABA-B-R1 abolished the antioxidant effects, and knockdown of CG6293 eliminated the antidepressant effects, implicating these genes as key downstream effectors. Supplementation with L-ascorbic acid mimicked the behavioral and oxidative resilience conferred by C. pluricaulis. Together, these findings reveal conserved antioxidant and anxiolytic mechanisms underlying the pharmacological effects of C. pluricaulis in Drosophila.
{"title":"Convolvulus pluricaulis confers antidepressant and antioxidant effects through conserved metabolic and molecular pathways in Drosophila","authors":"Shreyasi Mitra , Amit Kumar , Manish Pandey , Aman Gill , Meenakshi Sharma , Shivani Pundir , Mansi Jangir , Geetanjali Chawla","doi":"10.1016/j.isci.2025.114296","DOIUrl":"10.1016/j.isci.2025.114296","url":null,"abstract":"<div><div><em>Convolvulus pluricaulis</em> (shankhpushpi) is a traditional herb used to treat depression and anxiety. Using <em>Drosophila melanogaster</em> as a model, we identified conserved metabolic and molecular pathways mediating its neuroprotective effects. Metabolomic profiling of flies fed <em>C. pluricaulis</em> revealed altered levels of ascorbic acid, glucose, and adenine monophosphate in the head tissue. Gene expression analysis showed significant modulation of <em>G</em><em>lut1</em> (glucose transporter 1), <em>CG6293</em> (ascorbate transporter), <em>Rdl</em> (resistant to dieldrin), <em>GABA-B-R1</em> (GABA-B receptor 1), and <em>S</em><em>od1</em> (superoxide dismutase 1). Dietary <em>C. pluricaulis</em> reduced depression-like behavior in a stress-induced model and elevated head ascorbate levels. Knockdown of <em>CG6293</em>, <em>S</em><em>od1</em>, <em>G</em><em>lut1</em>, or <em>GABA-B-R1</em> abolished the antioxidant effects, and knockdown of <em>CG6293</em> eliminated the antidepressant effects, implicating these genes as key downstream effectors. Supplementation with L-ascorbic acid mimicked the behavioral and oxidative resilience conferred by <em>C. pluricaulis</em>. Together, these findings reveal conserved antioxidant and anxiolytic mechanisms underlying the pharmacological effects of <em>C. pluricaulis</em> in <em>Drosophila</em>.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"29 1","pages":"Article 114296"},"PeriodicalIF":4.1,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145788910","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Differential long non-coding RNA (lncRNA) expression has been correlated to clinical characteristics of colorectal cancers (CRCs), which are the second leading cause of cancer-related deaths. LncRNA UCA1 plays a role in epigenetic gene regulation in diverse cancers. We studied CRC cell properties in CRISPR-Cas9 HT29-derived models and, interestingly, UCA1-depleted HT29 cells presented an increased stem-cell phenotype. We show that loss of UCA1 modulated SWI/SNF chromatin remodeling complexes, previously shown to be involved in maintaining stem-cell properties. Not only was UCA1 permissive for induced SWI/SNF subunit SMARCA2 (BRM) expression upon chemo-drug treatment, but it also affected subunit compositions of SWI/SNF complexes by direct interaction of UCA1 with both ATP helicase BRM and BRG1. UCA1 is known to stimulate proliferation and decrease apoptosis, and we here show that it can restrain cells from a stem cell phenotype. The dual action of UCA1 revealed in this study highlights the complex actions of lncRNAs in cancer.
{"title":"Long non-coding RNA UCA1 modulates SMARCA2-containing SWI/SNF chromatin remodeling complexes in human colorectal cancer","authors":"Bernadette Neve , Elsa Hadj Bachir , Belinda Duchêne , Mouloud Souidi , Martin Figeac , Jean-Pascal Meneboo , Emmanuelle Leteurtre","doi":"10.1016/j.isci.2025.114283","DOIUrl":"10.1016/j.isci.2025.114283","url":null,"abstract":"<div><div>Differential long non-coding RNA (lncRNA) expression has been correlated to clinical characteristics of colorectal cancers (CRCs), which are the second leading cause of cancer-related deaths. LncRNA UCA1 plays a role in epigenetic gene regulation in diverse cancers. We studied CRC cell properties in CRISPR-Cas9 HT29-derived models and, interestingly, UCA1-depleted HT29 cells presented an increased stem-cell phenotype. We show that loss of UCA1 modulated SWI/SNF chromatin remodeling complexes, previously shown to be involved in maintaining stem-cell properties. Not only was UCA1 permissive for induced SWI/SNF subunit SMARCA2 (BRM) expression upon chemo-drug treatment, but it also affected subunit compositions of SWI/SNF complexes by direct interaction of UCA1 with both ATP helicase BRM and BRG1. UCA1 is known to stimulate proliferation and decrease apoptosis, and we here show that it can restrain cells from a stem cell phenotype. The dual action of UCA1 revealed in this study highlights the complex actions of lncRNAs in cancer.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"29 1","pages":"Article 114283"},"PeriodicalIF":4.1,"publicationDate":"2025-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145837607","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-29DOI: 10.1016/j.isci.2025.114272
Fei Guo , Nannan Liu , Ruiheng Peng , Binyao Wang , Yeqing Chang , Hong Jin , Xinyu Xiong , Dongxu Zhang , Qianlong Zhang , Liqiang Zheng
As one of the prevalent complications during pregnancy, this study discussed the association between gestational diabetes mellitus (GDM) and multi-source built-environment from the perspective of different spatial scales in mega-cities. This study centered on 4,355 women at a Shanghai hospital. Thirteen variables were selected, then multi-scale geographically weighted regression (MGWR) was used to clarity how these variables relate to GDM. The results showed that: MGWR effectively revealed the relationship between the built environment and GDM at different scales. At specific spatial scales, building-density (BD) and sky view factor (SVF) exhibit pronounced spatial heterogeneity. Based on the mean coefficients in MGWR, it can be inferred that for every 0.1 increase in SVF and green view index (GVI), the probability of GDM decreases by 3% and 1%. These findings delve into the association between the built environment and lifestyle-related diseases. They underscore the significance of developing place-specific policies in health interventions and urban planning.
{"title":"How does high-density built-environment affect the incidence of gestational diabetes mellitus","authors":"Fei Guo , Nannan Liu , Ruiheng Peng , Binyao Wang , Yeqing Chang , Hong Jin , Xinyu Xiong , Dongxu Zhang , Qianlong Zhang , Liqiang Zheng","doi":"10.1016/j.isci.2025.114272","DOIUrl":"10.1016/j.isci.2025.114272","url":null,"abstract":"<div><div>As one of the prevalent complications during pregnancy, this study discussed the association between gestational diabetes mellitus (GDM) and multi-source built-environment from the perspective of different spatial scales in mega-cities. This study centered on 4,355 women at a Shanghai hospital. Thirteen variables were selected, then multi-scale geographically weighted regression (MGWR) was used to clarity how these variables relate to GDM. The results showed that: MGWR effectively revealed the relationship between the built environment and GDM at different scales. At specific spatial scales, building-density (BD) and sky view factor (SVF) exhibit pronounced spatial heterogeneity. Based on the mean coefficients in MGWR, it can be inferred that for every 0.1 increase in SVF and green view index (GVI), the probability of GDM decreases by 3% and 1%. These findings delve into the association between the built environment and lifestyle-related diseases. They underscore the significance of developing place-specific policies in health interventions and urban planning.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"29 1","pages":"Article 114272"},"PeriodicalIF":4.1,"publicationDate":"2025-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145788830","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-29DOI: 10.1016/j.isci.2025.114271
Ravikumar Thangavel , Kalainathan Sivaperuman , Logu Thirumalaisamy , Christina Josephine Malathi A , Saravanan Pandiaraj , Maha Alruwaili , Nadyah Alanazi , Abdullah N. Alodhayb , R. Ramesh , Chamil Abeykoon , Andrews Nirmala Grace
This study focuses on developing economical and efficient ammonia (NH3) gas sensors capable of detecting low concentrations at room temperature. Cd-doped ZnFe2O4 (CdxZn1-xFe2O4, x = 0, 0.1,0.3, and 0.5) thin films were deposited via spray pyrolysis, showing significantly enhanced sensing performance compared to undoped ZnFe2O4. The Cd0.5Zn0.5Fe2O4 (ZFCD5) film demonstrated the best response (∼8) at 1 ppm NH3, with fast response (105 s) and recovery (54 s) times, a sensitivity of 10.07 ppm-1, repeatability, selectivity, and more stability over 6 weeks. The improved sensing is attributed to the angular-rod-like morphology that increases active sites and enhances charge transfer. Cd incorporation effectively boosts defect density and adsorption-desorption efficiency, resulting in a 10-fold higher response than the undoped film (∼0.8). The findings highlight the potential of Cd-doped ZnFe2O4 thin films as promising, room temperature NH3 sensors for industrial, environmental, and safety applications, also supporting safer environments for individuals with disabilities.
{"title":"Trace level detection of NH3 at room temperature using Cd-ZnFe2O4 thin films","authors":"Ravikumar Thangavel , Kalainathan Sivaperuman , Logu Thirumalaisamy , Christina Josephine Malathi A , Saravanan Pandiaraj , Maha Alruwaili , Nadyah Alanazi , Abdullah N. Alodhayb , R. Ramesh , Chamil Abeykoon , Andrews Nirmala Grace","doi":"10.1016/j.isci.2025.114271","DOIUrl":"10.1016/j.isci.2025.114271","url":null,"abstract":"<div><div>This study focuses on developing economical and efficient ammonia (NH<sub>3</sub>) gas sensors capable of detecting low concentrations at room temperature. Cd-doped ZnFe<sub>2</sub>O<sub>4</sub> (Cd<sub>x</sub>Zn<sub>1-x</sub>Fe<sub>2</sub>O<sub>4</sub>, x = 0, 0.1,0.3, and 0.5) thin films were deposited via spray pyrolysis, showing significantly enhanced sensing performance compared to undoped ZnFe<sub>2</sub>O<sub>4</sub>. The Cd<sub>0.5</sub>Zn<sub>0.5</sub>Fe<sub>2</sub>O<sub>4</sub> (ZFCD5) film demonstrated the best response (∼8) at 1 ppm NH<sub>3</sub>, with fast response (105 s) and recovery (54 s) times, a sensitivity of 10.07 ppm<sup>-1</sup>, repeatability, selectivity, and more stability over 6 weeks. The improved sensing is attributed to the angular-rod-like morphology that increases active sites and enhances charge transfer. Cd incorporation effectively boosts defect density and adsorption-desorption efficiency, resulting in a 10-fold higher response than the undoped film (∼0.8). The findings highlight the potential of Cd-doped ZnFe<sub>2</sub>O<sub>4</sub> thin films as promising, room temperature NH<sub>3</sub> sensors for industrial, environmental, and safety applications, also supporting safer environments for individuals with disabilities.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"29 1","pages":"Article 114271"},"PeriodicalIF":4.1,"publicationDate":"2025-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145788449","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-29DOI: 10.1016/j.isci.2025.114281
Reza Mirzaei , Reid McNeil , Charlotte D'Mello , Britney Wong , Susobhan Sarkar , Frank Visser , Candice Poon , Pinaki Bose , V. Wee Yong
Glioblastoma (GBM) contains diverse immune and tumor cell populations whose spatial organization influences disease progression. To better understand how immune cells interact with brain tumor-initiating cells (BTICs), we applied integrated single-cell and spatial transcriptomic approaches to map the immune landscape in a GBM mouse model. This analysis revealed a distinct subset of microglia expressing protein kinase Cδ (PKCδ) that localizes near BTIC-rich regions and displays features associated with anti-tumor activity. We validated the presence of PKCδ+ microglia in human GBM tissues and found that PKCδ enhances inducible nitric oxide synthase (iNOS) expression, supporting microglial cytotoxic and phagocytic functions. Increasing PKCδ levels in microglia, either through adeno-associated viral delivery or niacin treatment, strengthened their ability to engulf and kill BTICs. Analysis of patient datasets further showed that higher PKCδ expression associates with immune activation and cell death pathways. These findings identify PKCδ+ microglia as a therapeutically relevant component of the GBM microenvironment.
{"title":"Spatial single-cell profiling identifies protein kinase Cδ-expressing microglia with anti-tumor function in glioblastoma","authors":"Reza Mirzaei , Reid McNeil , Charlotte D'Mello , Britney Wong , Susobhan Sarkar , Frank Visser , Candice Poon , Pinaki Bose , V. Wee Yong","doi":"10.1016/j.isci.2025.114281","DOIUrl":"10.1016/j.isci.2025.114281","url":null,"abstract":"<div><div>Glioblastoma (GBM) contains diverse immune and tumor cell populations whose spatial organization influences disease progression. To better understand how immune cells interact with brain tumor-initiating cells (BTICs), we applied integrated single-cell and spatial transcriptomic approaches to map the immune landscape in a GBM mouse model. This analysis revealed a distinct subset of microglia expressing protein kinase Cδ (PKCδ) that localizes near BTIC-rich regions and displays features associated with anti-tumor activity. We validated the presence of PKCδ<sup>+</sup> microglia in human GBM tissues and found that PKCδ enhances inducible nitric oxide synthase (iNOS) expression, supporting microglial cytotoxic and phagocytic functions. Increasing PKCδ levels in microglia, either through adeno-associated viral delivery or niacin treatment, strengthened their ability to engulf and kill BTICs. Analysis of patient datasets further showed that higher PKCδ expression associates with immune activation and cell death pathways. These findings identify PKCδ<sup>+</sup> microglia as a therapeutically relevant component of the GBM microenvironment.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"29 1","pages":"Article 114281"},"PeriodicalIF":4.1,"publicationDate":"2025-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145788980","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-29DOI: 10.1016/j.isci.2025.114276
Sumaya Mahomed , Rebekah Shirley , Carolina Ines Pan
Despite global progress, the energy access gap in sub-Saharan Africa is widening. African utilities contend with limited capital, low customer density, weak purchasing power, and high losses, while decentralized renewable energy (DRE) developers face challenges of raising capital, operational sustainability, and regulatory barriers. Integrated energy models that leverage utility grid assets and DRE innovation promise comparative advantages, yet implementation cases are scarce. This paper presents a five-year study (2018–2023) conducted in Mukono District, Uganda, involving Umeme and a consortium of DRE service providers. We detail partnership structure, integration approach, performance metrics, and outcomes for customers, the utility, and developers. In this study, the integrated model outpaced the standard grid extension approach in establishing new connections, delivered a large increase in household and business consumption, and reduced the overall connection cost. These findings have important implications for scalable pathways to advance resilient, universal energy access under SDG7 by 2030.
{"title":"Integrated energy in action: Practical learnings from integrating centralized and decentralized energy delivery models in Uganda","authors":"Sumaya Mahomed , Rebekah Shirley , Carolina Ines Pan","doi":"10.1016/j.isci.2025.114276","DOIUrl":"10.1016/j.isci.2025.114276","url":null,"abstract":"<div><div>Despite global progress, the energy access gap in sub-Saharan Africa is widening. African utilities contend with limited capital, low customer density, weak purchasing power, and high losses, while decentralized renewable energy (DRE) developers face challenges of raising capital, operational sustainability, and regulatory barriers. Integrated energy models that leverage utility grid assets and DRE innovation promise comparative advantages, yet implementation cases are scarce. This paper presents a five-year study (2018–2023) conducted in Mukono District, Uganda, involving Umeme and a consortium of DRE service providers. We detail partnership structure, integration approach, performance metrics, and outcomes for customers, the utility, and developers. In this study, the integrated model outpaced the standard grid extension approach in establishing new connections, delivered a large increase in household and business consumption, and reduced the overall connection cost. These findings have important implications for scalable pathways to advance resilient, universal energy access under SDG7 by 2030.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"29 1","pages":"Article 114276"},"PeriodicalIF":4.1,"publicationDate":"2025-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145837618","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}